Possible involvement of nitrergic and opioidergic systems in the modulatory effect of acute chloroquine treatment on pentylenetetrazol induced convulsions in mice
| Autor: | Nastaran Rahimi, Sattar Ostadhadi, Mahsa Hassanipour, Shayan Amiri, Sina Delazar, Armin Shirzadian, Alireza Abkhoo, Ahmad Reza Dehpour, Aminreza Abkhoo, Mahdi Mashhadi Akbar Boojar |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Indazoles Time Factors medicine.medical_treatment Pharmacology Arginine Nitric Oxide Guanidines Hippocampus Naltrexone 03 medical and health sciences Mice 0302 clinical medicine Chloroquine Seizures medicine Animals Pentylenetetrazol Enzyme Inhibitors Nitrites Endogenous opioid Opioidergic Analysis of Variance Seizure threshold Dose-Response Relationship Drug business.industry General Neuroscience Effective dose (pharmacology) Analgesics Opioid Disease Models Animal 030104 developmental biology Anticonvulsant NG-Nitroarginine Methyl Ester Pentylenetetrazole Anticonvulsants Nitric Oxide Synthase business 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Brain research bulletin. 121 |
| ISSN: | 1873-2747 |
| Popis: | Chloroquine has long been used for the treatment of malaria and rheumatological disorders. Accumulating evidence suggests potential use of chloroquine as a neuroprotective agent. Several studies have reported that endogenous opioids and nitric oxide (NO) system mediate the chloroquine effects. In the present study, the involvements of endogenous opioids and NO in the modulatory effects of chloroquine on pentylenetetrazol-induced seizures were assessed in mice. Chloroquine 5mg/kg significantly increased the seizure threshold, but this effect was reversed with naltrexone 1mg/kg. Acute co-administration of l-NAME (non-selective NO synthase (NOS) inhibitor, 5mg/kg) or 7-NI (selective neuronal NOS inhibitor, 40 mg/kg) with the effective dose of chloroquine completely inhibited its anticonvulsant effects. Acute single injection of a sub-effective dose of l-arginine (NO precursor, 60 mg/kg) with a sub-effective dose of chloroquine 2.5mg/kg increased the seizure threshold but administration of L-arginine 60 mg/kg with chloroquine 10mg/kg decreased the seizure threshold. Moreover, the combination of the lower doses of naltrexone (0.1mg/kg) and 7-NI (15 mg/kg) showed additive effects in blocking the chloroquine-induced anticonvulsant properties. Chloroquine 5mg/kg enhanced the hippocampal nitrite levels. Chloroquine at the dose of 20mg/kg decreased the seizure threshold. This effect was inhibited through L-NAME (5mg/kg), 7-NI (40 mg/kg) and naltrexone (1mg/kg) administration with this dose of chloroquine. In conclusion, NO signaling probably through neuronal NOS, but not inducible NOS could be involved in the opioid-dependent anticonvulsant effects of chloroquine in this model of seizures in mice. It seems that nitric oxide and opioid systems are involved in modulatory effect of chloroquine on seizures induced by pentylenetetrazol. |
| Databáze: | OpenAIRE |
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